Multisize Electrode Field-of-View: Validation by High Resolution Gadolinium-Enhanced Cardiac Magnetic Resonance.

BACKGROUND: Voltage mapping to detect ventricular scar is important for guiding catheter ablation, but the field-of-view of unipolar, bipolar, conventional, and microelectrodes as it relates to the extent of viable myocardium (VM) is not well defined. OBJECTIVES: The purpose of this study was to evaluate electroanatomic voltage-mapping (EAVM) with different-size electrodes for identifying VM, validated against high-resolution ex-vivo cardiac magnetic resonance (HR-LGE-CMR). METHODS: A total of 9 swine with early-reperfusion myocardial infarction were mapped with the QDOT microcatheter. HR-LGE-CMR (0.3-mm slices) were merged with EAVM. At each EAVM point, the underlying VM in multisize transmural cylinders and spheres was quantified from ex vivo CMR and related to unipolar and bipolar voltages recorded from conventional and microelectrodes. RESULTS: In each swine, 220 mapping points (Q1, Q3: 216, 260 mapping points) were collected. Infarcts were heterogeneous and nontransmural. Unipolar and bipolar voltage increased with VM volumes from >175 mm3 up to >525 mm3 (equivalent to a 5-mm radius cylinder with height >6.69 mm). VM volumes in subendocardial cylinders with 1- or 3-mm depth correlated poorly with all voltages. Unipolar voltages recorded with conventional and microelectrodes were similar (difference 0.17 ± 2.66 mV) and correlated best to VM within a sphere of radius 10 and 8 mm, respectively. Distance-weighting did not improve the correlation. CONCLUSIONS: Voltage increases with transmural volume of VM but correlates poorly with small amounts of VM, which limits EAVM in defining heterogeneous scar. Microelectrodes cannot distinguish thin from thick areas of subendocardial VM. The field-of-view for unipolar recordings for microelectrodes and conventional electrodes appears to be 8 to 10 mm, respectively, and unexpectedly similar.

A Comprehensive Overview of the Neural Mechanisms of Light Therapy.

Light is a powerful environmental factor influencing diverse brain functions. Clinical evidence supports the beneficial effect of light therapy on several diseases, including depression, cognitive dysfunction, chronic pain, and sleep disorders. However, the precise mechanisms underlying the effects of light therapy are still not well understood. In this review, we critically evaluate current clinical evidence showing the beneficial effects of light therapy on diseases. In addition, we introduce the research progress regarding the neural circuit mechanisms underlying the modulatory effects of light on brain functions, including mood, memory, pain perception, sleep, circadian rhythm, brain development, and metabolism.

Increased functional connectivity between the midbrain and frontal cortex following bright light therapy in subthreshold depression: A randomized clinical trial.

The underlying mechanisms of bright light therapy (BLT) in the prevention of individuals with subthreshold depression symptoms are yet to be elucidated. The goal of the study was to assess the correlation between midbrain monoamine-producing nuclei treatment-related functional connectivity (FC) changes and depressive symptom improvements in subthreshold depression. This double-blind, randomized, placebo-controlled clinical trial was conducted between March 2020 and June 2022. A total of 74 young adults with subthreshold depression were randomly assigned to receive 8-week BLT (N = 38) or placebo (N = 36). Depression severity was measured using the Hamilton Depression Rating Scale (HDRS). The participants underwent resting-state functional magnetic resonance imaging at baseline and after treatment. The dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and habenula seed-based whole-brain FC were analyzed. A multivariate regression model examined whether baseline brain FC was associated with changes in scores on HDRS during BLT treatment. BLT group displayed significantly decreased HDRS scores from pre- to posttreatment compared to the placebo group. BLT increased the FC between the DRN and medial prefrontal cortex (mPFC) and between the left VTA and right superior frontal gyrus (SFG). Altered VTA-SFG connectivity was associated with HDRS changes in the BLT group. Moreover, the baseline FC between DRN and mPFC could predict HDRS changes in BLT. These results suggested that BLT improves depressive symptoms and increases midbrain monoamine-producing nuclei and frontal cortex connectivity in subthreshold depression, which raises the possibility that pretreatment FC of DRN-mPFC could be used as a biomarker for improved BLT treatment in depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A visual circuit related to the habenula mediates the prevention of cocaine relapse by bright light treatment.

Despite significant advancements in our understanding of addiction at the neurobiological level, a highly effective extinction procedure for preventing relapse remains elusive. In this study, we report that bright light treatment (BLT) administered during cocaine withdrawal with extinction training prevents cocaine-driven reinstatement by acting through the thalamic-habenular pathway. We found that during cocaine withdrawal, the lateral habenula (LHb) was recruited, and inhibition of the LHb via BLT prevented cocaine-driven reinstatement. We also demonstrated that the effects of BLT were mediated by activating LHb-projecting neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL) or by inhibiting postsynaptic LHb neurons. Furthermore, BLT was found to improve aversive emotional states induced by drug withdrawal. Our findings suggest that BLT administered during the cocaine withdrawal may be a promising strategy for achieving drug abstinence.

Selenite as a dual apoptotic and ferroptotic agent synergizes with EGFR and KRAS inhibitors with epigenetic interference.

BACKGROUND: Selenium, an essential trace element, has previously been investigated as a pro-apoptotic and DNA demethylation agent. It sensitizes the response to chemotherapy in patients who were refractory to cytotoxic agents. Meanwhile, ferroptosis is a novel approach to cancer treatment by triggering cell death and reversing drug resistance. The role of selenium in treating cancer cells harboring druggable oncogenic alterations and its underlying mechanism are largely unknown. RESULTS: We treated lung adenocarcinoma cell lines-EGFR-mutant H1975 (H1975 EGFR p.L858R and p.T790M) and KRAS-mutant H358 (H358 KRAS p.G12C), with sodium selenite to examine its effect on cell apoptosis, ferroptosis, and DNA methylation, as well as its interaction with existing targeted therapy, osimertinib, and adagrasib. We observed selenite to be a dual apoptotic and ferroptotic agent on lung cancer cells, associated with the activation of p38-ATF4-DDIT3 axis in the unfolded protein response. Ferroptosis induction was more remarkable in H1975 than H358. Selenite also altered cellular DNA methylation machinery through downregulating DNMT1 and upregulating TET1, though not as a major mechanism of its activity. Low-dose selenite synergized with osimertinib in EGFR-mutant H1975, and with adagrasib in KRAS-mutant H358, with stronger synergism observed in H1975. CONCLUSION: These results suggest that selenite is a potential apoptotic and ferroptotic drug candidate for the treatment of especially EGFR- and potentially KRAS-mutant lung cancer.

Supplementation with α-ketoglutarate improved the efficacy of anti-PD1 melanoma treatment through epigenetic modulation of PD-L1.

Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG's function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.

Randomized trial estimating effects of hypnosis versus progressive muscle relaxation on medical students' test anxiety and attentional bias.

BACKGROUND: Test anxiety is prevalent among medical students and leads to impaired academic performance. Test-related attentional bias has been identified as an important maintaining factor in test-anxious individuals. AIM: To evaluate whether hypnosis and progressive muscle relaxation (PMR) could modify medical college students' test anxiety and attentional bias. METHODS: A total of 598 medical students were screened. The participants were divided into higher and lower test anxiety groups according to their scores on the test anxiety scale (TAS). Ninety medical college students with high TAS score were randomly assigned to a hypnosis or PMR group. Another 45 students with low TAS score were included, forming a baseline control group. The intervention was conducted weekly for 6 wk, and each session lasted approximately 30 min. The total intervention time and the number of intervention sessions for the hypnosis and PMR groups were equal. Data were collected at the pretest, posttest, and 2-mo follow-up. RESULTS: Hypnosis group participants had a significantly lower TAS score at posttest (t = -21.827, P < 0.001) and at follow-up (t = -14.824, P < 0.001), compared to that at pretest. PMR group participants also had a significantly lower TAS score at posttest (t = -10.777, P < 0.001) and at follow-up (t = -7.444, P < 0.001), compared to that at pretest. At the posttest level, the hypnosis group had a significantly lower TAS score than the PMR group (t = -3.664, P < 0.001). At the follow-up level, the hypnosis group also had a significantly lower TAS score than the PMR group (t = -2.943, P = 0.004). Clinically significant improvement was found in both the hypnosis and PMR groups (hypnosis = 64.0%; PMR = 62.22%). Hypnosis was more effective than PMR in reducing test anxiety among medical college students. Hypnosis could modify attentional bias toward threatening stimuli, but PMR could not. CONCLUSION: These results suggest that attentional bias plays an important role in test anxiety treatment.

Genotoxicity, acute and subchronic toxicity evaluation of fermented Morinda officinalis.

Morinda officinalis has diverse pharmacological effects and has the potential to be used as functional food and medicine. Fermentation is traditionally used to process Morinda officinalis. However, the toxicological profile of fermented Morinda officinalis (FMO) is not reported. In the present study, the toxicological characteristics of FMO were assessed for the first time. FMO did not show any genotoxicity based on the Ames test, mammalian erythrocyte micronucleus test, and mouse primary spermatocyte chromosome aberration test. FMO administered by gavage in mice and rats at a dose of 20 g/kg BW did not induce death or toxicity based on acute study, indicating that FMO could be regarded as non-toxic at the tested dose. In the 90-day subchronic toxicity study, rats fed with FMO at the maximum dose of 8 g/kg BW did not affect mortalities, BW, food consumption, organ weights, hematology, serum biochemistry, or urinalysis. The no observed adverse effect level of FMO in both sexes was not less than 8 g/kg BW/day based on subchronic toxicity. The obtained results support the safe use of FMO as functional food and medicine.

Effects of different harvesting times and processing methods on the quality of cultivated Fritillaria cirrhosa D. Don.

Fritillaria cirrhosa D. Don is the major source plants of traditional Chinese medicine Fritillariae Cirrhosae Bulbus (FCB). Domestication, introduction, and cultivation is an important strategy to alleviate the shortage of endangered medicinal plants of F. cirrhosa. However, until now, the yield and quality changes of FCB in different harvest periods and drying treatments after harvest were not well understood. Therefore, in this paper, we investigated the yield and quality of cultivated F. cirrhosa at different harvest periods and postharvest processing methods. The results showed that dry weight per bulb ranged from 0.8913 to 1.4681 g and reached the highest at the wilting stage. The soluble sugar content ranged from 0.075% to 0.127% and reached the highest at the wilting stage. The content of total alkaloids ranged from 0.088% to 0.218% and reached the highest at the late-flowering stage. The contents of peimisine, sipeimine, peimine, and peiminine were 0.01178%-0.02615%, 0%-0.01713%, 0%-0.00745%, and 0%-0.00621% and reached the highest at the late-flowering period, wilting period, young fruit period, and initial flowering period, respectively. For the two different postharvest processing methods, the contents of total alkaloids and the 16 main characteristic peaks did not exhibit significant differences. Still, the alkaloid contents of the oven drying after washing were slightly higher than the sun drying. In conclusion, the best harvest period is the wilting period of F. cirrhosa, and oven drying after washing is more beneficial to ensure the quality of FCB and improve productivity.

Mini-, Micro-, and Conventional Electrodes: An in Vivo Electrophysiology and Ex Vivo Histology Head-to-Head Comparison.

OBJECTIVES: This study sought to assess the relative effect of catheter, tissue, and catheter-tissue parameters, on the ability to determine the amount of viable myocardium in vivo. BACKGROUND: Although multiple variables impact bipolar voltages (BVs), electrode size, interelectrode spacing, and directional dependency are of particular interest with the development of catheters incorporating mini and microelectrodes. METHODS: Nine swine with early reperfusion myocardial infarctions were mapped using the QDot catheter and then remapped using a Pentaray catheter. All QDot points were matched with Pentaray points within 5 mm. The swine were sacrificed, and mapping data projected onto the heart. Transmural biopsies corresponding to mapping points were obtained, allowing a comparison of electrograms recorded by mini, micro-, and conventional electrodes with histology. RESULTS: The conventional BV of 2,322 QDot points was 1.9 ± 1.3 mV. The largest of the 3 microelectrode BVs (BVµMax) average 4.8 ± 3.1 mV. The difference between the largest (BVµMax) and smallest (BVµMin) at a given location was 53.7 ± 18.1%. The relationships between both BVµMax and BVµMin and between the conventional BV and BVµMax were positively related but with a significant spread in data, which was more pronounced for the latter. Pentaray points positively related to the BVµMax with poor fit. On histology, increasing viable myocardium increased voltage, but both the slope coefficient and fit were best for BVµMax. CONCLUSIONS: Using histology, we could demonstrate that BVµMax is superior to identify viable myocardium compared with BVC and BV using the Pentaray catheter. The ability to simultaneously record 3 BVµs with different orientations, for the same beat, with controllable contact and selecting BVµMax for local BV may partially compensate for wave front direction.

Efficacy of light therapy for a college student sample with non-seasonal subthreshold depression: An RCT study.

BACKGROUND: Light therapy has been successfully used to treat seasonal and non-seasonal depression, but there is limited evidence for its efficacy in subthreshold depression. This study examines the efficacy of light therapy for symptoms of depression and anxiety in non-seasonal subthreshold depression. METHODS: College students with non-seasonal subthreshold depression were recruited. The participants were randomly allocated to one of the three conditions: high- (LT-5000 lux) and low-intensity (LT-500 lux) light therapy conditions and a waiting-list control condition (WLC). The primary outcome was Hamilton Depression Rating Scale (HAMD), and secondary outcomes were Beck Depression Inventory-II (BDI-II) and state anxiety inventory (SAI), which were assessed at baseline (Week 0), during the trial (Week 4), and after completion of the light therapy (Week 8). RESULTS: A total of 142 participants completed the trial. The LT-5000 (effect size [d] = 1.56, 95% CI: 1.15 to 1.98) and LT-500 conditions (d = 0.84, 95% CI: 0.43 to 1.26) were significantly superior to the WLC condition. For the LT-5000, LT-500, and WLC conditions by the end of the 8-week trial, a response on the HAMD was achieved by 70.0%, 42.0% and 19.0% of the participants, and remission was achieved by 76.0%, 54.0%, and 19.0%, respectively. LIMITATIONS: The subjects were not followed up regularly after completion of the trial. CONCLUSION: Light therapy, both at high- and low-intensity, was efficacious in the treatment of college students with non-seasonal subthreshold depression. High-intensity light therapy was superior to low-intensity light therapy by the end of an 8-week trial.

Multisize Electrodes for Substrate Identification in Ischemic Cardiomyopathy: Validation by Integration of Whole Heart Histology.

OBJECTIVES: This study sought to evaluate the value of combined electrogram (EGM) information provided by simultaneous mapping using micro- and conventional electrodes in the identification of post-myocardial infarction ventricular tachycardia substrate. BACKGROUND: Ventricular tachycardias after myocardial infarction are related to scars with complex geometry. Scar delineation and ventricular tachycardia substrate identification relies on bipolar voltages (BV) and EGM characteristics. Early reperfusion therapy results in small, nontransmural scars, the details of which may not be delineated using 3.5 mm tip catheters. METHODS: Nine swine with early reperfusion myocardial infarction were mapped using Biosense Webster's QDOT Micro catheter, incorporating 3 microelectrodes at the tip of the standard 3.5 mm electrode. Analysis of EGM during sinus rhythm, right ventricular pacing, and short-coupled right ventricular extrastimuli was performed. The swine were sacrificed and mapping data were projected onto the heart. Transmural biopsies (n = 196) corresponding to mapping points were obtained, allowing a head-to-head comparison of EGM recorded by micro- and conventional electrodes with histology. RESULTS: To identify scar areas using standard electrodes, unique cutoff values of unipolar voltage <5.44 mV, BV <1.27 mV (conventional), and BV <2.84 mV (microelectrode) were identified. Combining the information provided by unipolar voltage and BV mapping, the sensitivity of scar identification was increased to 93%. Micro-EGM were better able to distinguish small near-fields corresponding to a layer of viable subendocardium than conventional EGM were. CONCLUSIONS: The combined information provided by multisize electrode mapping increases the sensitivity with which areas of scar are identified. EGM from microelectrodes, with narrower spacing, allow identification of near-fields arising from thin subendocardial layer and layers activated with short delay obscured in EGM from conventional mapping catheter.

Impact of traditional Chinese medicine treatment on chronic unpredictable mild stress-induced depression-like behaviors: intestinal microbiota and gut microbiome function.

Gut microbiota dysbiosis is a recognized contributing factor to many noncommunicable diseases, but more evidence is still needed to illustrate its causative impact on mental and brain health disorders and mechanism(s) for targeted mitigation. Traditional Chinese Medicine (TCM) has been used in the management of neuropsychiatric diseases for many years in China. In this study, a randomized, controlled trial was conducted to examine the impact of stress on gut microbiota dysbiosis and depression, and TCM in alleviating the damage using Chronic Unpredictable Mild Stress (CUMS) rats, a well-established rodent model for depression. The behaviors of rats and the profiles of the fecal microbiota were assessed by an array of behavioral tests and 16S rRNA gene sequencing, and the intestinal microbial function was assessed by shotgun sequencing-based metagenomic analysis of microbial DNA from fecal samples. Data on brain targeted metabolites by liquid chromatography-mass spectrometry (LC-MS) were also discussed. Depressive and anxiety-like behaviors and changes in the fecal microbiota profile were observed in CUMS rats, which were then significantly reversed in CUMS rats that received TCM. Specifically, TCM treatment reduced the levels of Firmicutes, and Ruminococcus, and increased the abundance of Bacteroidetes and Roseburia, reportedly being associated with relieving psychiatric disorders. Furthermore, the levels of brain metabolites perturbed by CUMS were reversed by TCM treatment, and Spearman's correlation analysis illustrated strong correlation between brain metabolites and perturbed fecal microbiota genera. Finally, the fecal microbiome of CUMS rats was characterized by alterations in amino acid metabolism and evaluation of bile acid biosynthesis, and TCM-treated rats showed elevation of cysteine and methionine metabolism. Overall, these results indicated that administration of the TCM may mitigate CUMS-induced depression-behaviors, and it is correlated with reversing CUMS-induced intestinal microbiota dysbiosis; evidence also supported related changes in brain metabolites. These findings set up the foundation to further reveal the exact causal relationship among the TCM formula, host responses, gut microbiota dysbiosis and the levels of brain metabolites, and enabled scientific interpretation of the therapeutic function of the TCM.

A Visual Circuit Related to Habenula Underlies the Antidepressive Effects of Light Therapy.

Light plays a pivotal role in the regulation of affective behaviors. However, the precise circuits that mediate the impact of light on depressive-like behaviors are not well understood. Here, we show that light influences depressive-like behaviors through a disynaptic circuit linking the retina and the lateral habenula (LHb). Specifically, M4-type melanopsin-expressing retinal ganglion cells (RGCs) innervate GABA neurons in the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn inhibit CaMKIIα neurons in the LHb. Specific activation of vLGN/IGL-projecting RGCs, activation of LHb-projecting vLGN/IGL neurons, or inhibition of postsynaptic LHb neurons is sufficient to decrease the depressive-like behaviors evoked by long-term exposure to aversive stimuli or chronic social defeat stress. Furthermore, we demonstrate that the antidepressive effects of light therapy require activation of the retina-vLGN/IGL-LHb pathway. These results reveal a dedicated retina-vLGN/IGL-LHb circuit that regulates depressive-like behaviors and provide a potential mechanistic explanation for light treatment of depression.

Targeting the Hidden Substrate Unmasked by Right Ventricular Extrastimulation Improves Ventricular Tachycardia Ablation Outcome After Myocardial Infarction.

OBJECTIVES: This study sought to determine whether ablation of hidden substrate unmasked by right ventricular extrastimulation (RVE) improves ablation outcome of post-myocardial infarction (MI) ventricular tachycardia (VT). BACKGROUND: In patients with small or nontransmural scars after MI, part of the VT substrate may be functional and, in addition, masked by high-voltage far-field signals arising from adjacent normal myocardium. METHODS: In 60 consecutive patients, systematic analysis of electrograms recorded from the presumed infarct area was performed during sinus rhythm, RV pacing at 500 ms, and during a short-coupled RV extrastimulus. Sites showing low-voltage, near-field potentials with evoked conduction delay in response to RVE were targeted. RESULTS: In 37 (62%) patients, ablation target sites located in areas with normal voltage during sinus rhythm were unmasked by RVE (hidden substrate group). These patients had better left ventricular function (36 ± 11% vs. 26 ± 12%; p = 0.003), smaller electroanatomical scars (<1.5 mV), and smaller dense scars (<0.5 mV) (median 59 and 14 cm2 vs. 82 and 44 cm2; p = 0.044 and p = 0.003) than did those in whom no hidden substrate was identified (overt substrate group). During a median follow-up of 16 months, 13 (22%) patients had VT recurrence. Patients with hidden substrate had a lower incidence of VT recurrence (12-month VT-free survival 89% vs. 50% in patients with overt substrate; p = 0.005). Compared with a historical cohort of 90 post-MI patients matched for left ventricular function and electroanatomical scar area, in whom no RVE was performed, patients in the hidden substrate group had a higher 1-year VT-free survival (89% vs. 73%; p = 0.039). CONCLUSIONS: Hidden substrate ablation unmasked by RVE improves ablation outcome in post-MI patients with small or nontransmural scars.

A retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour.

Animals promote their survival by avoiding rapidly approaching objects that indicate threats. In mice, looming-evoked defensive responses are triggered by the superior colliculus (SC) which receives direct retinal inputs. However, the specific neural circuits that begin in the retina and mediate this important behaviour remain unclear. Here we identify a subset of retinal ganglion cells (RGCs) that controls mouse looming-evoked defensive responses through axonal collaterals to the dorsal raphe nucleus (DRN) and SC. Looming signals transmitted by DRN-projecting RGCs activate DRN GABAergic neurons that in turn inhibit serotoninergic neurons. Moreover, activation of DRN serotoninergic neurons reduces looming-evoked defensive behaviours. Thus, a dedicated population of RGCs signals rapidly approaching visual threats and their input to the DRN controls a serotonergic self-gating mechanism that regulates innate defensive responses. Our study provides new insights into how the DRN and SC work in concert to extract and translate visual threats into defensive behavioural responses.

How does experience modulate auditory spatial processing in individuals with blindness?

Comparing early- and late-onset blindness in individuals offers a unique model for studying the influence of visual experience on neural processing. This study investigated how prior visual experience would modulate auditory spatial processing among blind individuals. BOLD responses of early- and late-onset blind participants were captured while performing a sound localization task. The task required participants to listen to novel "Bat-ears" sounds, analyze the spatial information embedded in the sounds, and specify out of 15 locations where the sound would have been emitted. In addition to sound localization, participants were assessed on visuospatial working memory and general intellectual abilities. The results revealed common increases in BOLD responses in the middle occipital gyrus, superior frontal gyrus, precuneus, and precentral gyrus during sound localization for both groups. Between-group dissociations, however, were found in the right middle occipital gyrus and left superior frontal gyrus. The BOLD responses in the left superior frontal gyrus were significantly correlated with accuracy on sound localization and visuospatial working memory abilities among the late-onset blind participants. In contrast, the accuracy on sound localization only correlated with BOLD responses in the right middle occipital gyrus among the early-onset counterpart. The findings support the notion that early-onset blind individuals rely more on the occipital areas as a result of cross-modal plasticity for auditory spatial processing, while late-onset blind individuals rely more on the prefrontal areas which subserve visuospatial working memory.

CMR-based identification of critical isthmus sites of ischemic and nonischemic ventricular tachycardia.

OBJECTIVES: This study evaluates whether contrast-enhanced (CE) cardiac magnetic resonance (CMR) can be used to identify critical isthmus sites for ventricular tachycardia (VT) in ischemic and nonischemic heart disease. BACKGROUND: Fibrosis interspersed with viable myocytes may cause re-entrant VT. CE-CMR has the ability to accurately delineate fibrosis. METHODS: Patients who underwent VT ablation with CE-CMR integration were included. After the procedure, critical isthmus sites (defined as sites with a ≥11 of 12 pacemap, concealed entrainment, or VT termination during ablation) were projected on CMR-derived 3-dimensional (3D) scar reconstructions. The scar transmurality and signal intensity at all critical isthmus, central isthmus, and exit sites were compared to the average of the entire scar. The distance to >75% transmural scar and to the core-border zone (BZ) transition was calculated. The area within 5 mm of both >75% transmural scar and the core-BZ transition was calculated. RESULTS: In 44 patients (23 ischemic and 21 nonischemic, left ventricular ejection fraction 44 ± 12%), a total of 110 VTs were induced (cycle length 290 ± 67 ms). Critical isthmus sites were identified for 78 VTs (71%) based on ≥11 of 12 pacemaps (67 VTs), concealed entrainment (10 VTs), and/or termination (30 VTs). The critical isthmus sites, and in particular central isthmus sites, had high scar transmurality and signal intensity compared with the average of the entire scar. Of the pacemap, concealed entrainment, and termination sites, 74%, 100%, and 84% were within 5 mm of >75% transmural scar, and 67%, 100%, and 94% were within 5 mm of the core-BZ transition, respectively. The areas within 5 mm of both >75% transmural scar and the core-BZ transition (median 13% of LV) contained all concealed entrainment sites and 77% of termination sites. CONCLUSIONS: Both in ischemic and nonischemic VT, critical isthmus sites are typically located in close proximity to the CMR-derived core-BZ transition and to >75% transmural scar. These findings suggest that CMR-derived scar characteristics may guide to critical isthmus sites during VT ablation.

The molecular and electrophysiological mechanism of buyanghuanwu decoction in learning and memory ability of vascular dementia rats.

Buyanghuanwu Decoction (BYHWD), as a traditional Chinese medicine, has been developed to treat vascular dementia for hundreds of years, but the underlying mechanisms remain unknown. In this research, the protective effects of BYHWD on hippocampal neuron were examined in the rats of ischemia-reperfusion. Ischemia-reperfusion injury was induced by the four-vessel occlusion method and continued for 30 days. BYHWD (per 6.25g/kg/d) was orally given to rats twice each day for 30 days after ischemia-reperfusion, Nimodipine (per 10mg/kg/d) was orally given to rats twice each day for 30 days. In VD+BYHWD group rats, the neuronal injury in the hippocampal CA1 region was significantly less than that of VD group's. BYHWD of intragastric administration also markedly increased the expression of Extracellular signal-regulated kinase 2 (ERK2) and Calcium/calmodulin-dependent protein kinaseII (CaMKIIIy)in the CA1 region. Our results suggested that increased ERK2 and CaMKIIIy due to BYHWD may partially account for its effect of neuroprotection standing against ischemic injury in the hippocampal CA1 region, and participated in the rebuilding of synapse, strengthened the expression of LTP, promoted the ability recover of learning and memory in VD rats.

Contrast-enhanced MRI-derived scar patterns and associated ventricular tachycardias in nonischemic cardiomyopathy: implications for the ablation strategy.

BACKGROUND: There are limited data on typical arrhythmogenic substrates and associated ventricular tachycardias (VT) in patients with nonischemic cardiomyopathy. The substrate location may have implications for the ablation strategy. METHODS AND RESULTS: Nineteen consecutive patients with nonischemic cardiomyopathy (age 58±14 years, 79% men, left ventricular ejection fraction 41±11%) who underwent contrast-enhanced MRI and VT ablation were included. On the basis of 3-dimensional contrast-enhanced MRI-derived scar reconstructions, 8 patients (42%) had predominant basal anteroseptal scar, 9 patients (47%) had predominant inferolateral scar, and 2 patients (11%) had other scar types. Three distinct VT morphologies (≥1 of 3 inducible in 16/19 patients) were associated with underlying scar type. In 9 patients with anteroseptal scar-related VT (8/9 predominant scar, 1/9 nonpredominant), ablation target sites (defined as sites with ≥11/12 pacemap, concealed entrainment or VT termination during ablation) were located in the aortic root and/or anteroseptal left ventricular endocardium in 8 patients (89%) and in the anterior cardiac vein in 1 patient (11%), with additional target sites at the right ventricular septum in 2 patients (22%) and at the epicardium in 1 patient (11%). In contrast, in 8 patients with predominant inferolateral scar-related VT, target sites were located at the epicardium in 5 patients (63%) and in the endocardial inferolateral left ventricle in 3 patients (37%). CONCLUSIONS: Two typical scar patterns (anteroseptal and inferolateral) account for 89% of arrhythmogenic substrates in patients with nonischemic cardiomyopathy. Three distinct VT morphologies are highly suggestive of the presence of these scars. Anteroseptal scars were, in general, most effectively approached from the aortic root or anteroseptal left ventricular endocardium, whereas inferolateral scars frequently required an epicardial approach.